Activation of a Sweet Taste Receptor by Oleanane-Type Glycosides from Wisteria sinensis.

The phytochemical study of Wisteria sinensis (Sims) DC. (Fabaceae), commonly known as the Chinese Wisteria, led to the isolation of seven oleanane-type glycosides from an aqueous-ethanolic extract of the roots. Among the seven isolated saponins, two have never been reported before: 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl-(1→2)-ß-D-glucuronopyranosyl-22-O-acetylolean-12-ene-3ß,16ß,22ß,30-tetrol, and 3-O-ß-D-xylopyranosyl-(1→2)-ß-D-glucuronopyranosylwistariasapogenol A. Based on the close structures between the saponins from W. sinensis, and the glycyrrhizin from licorice, the stimulation of the sweet taste receptor TAS1R2/TAS1R3 by these glycosides was evaluated.

ß-Amyrin Synthase1 Controls the Accumulation of the Major Saponins Present in Pea (Pisum sativum).

The use of pulses as ingredients for the production of food products rich in plant proteins is increasing. However, protein fractions prepared from pea or other pulses contain significant amounts of saponins, glycosylated triterpenes that can impart an undesirable bitter taste when used as an ingredient in foodstuffs. In this article, we describe the identification and characterization of a gene involved in saponin biosynthesis during pea seed development, by screening mutants obtained from two Pisum sativum TILLING (Targeting Induced Local Lesions IN Genomes) populations in two different genetic backgrounds. The mutations studied are located in a gene designated PsBAS1 (ß-amyrin synthase1), which is highly expressed in maturing pea seeds and which encodes a protein previously shown to correspond to an active ß-amyrin synthase. The first allele is a nonsense mutation, while the second mutation is located in a splice site and gives rise to a mis-spliced transcript encoding a truncated, nonfunctional protein. The homozygous mutant seeds accumulated virtually no saponin without affecting the seed nutritional or physiological quality. Interestingly, BAS1 appears to control saponin accumulation in all other tissues of the plant examined. These lines represent a first step in the development of pea varieties lacking bitterness off-flavors in their seeds. Our work also shows that TILLING populations in different genetic backgrounds represent valuable genetic resources for both crop improvement and functional genomics.

Triterpenoid Saponins from the Cultivar "Green Elf" of Pittosporum tenuifolium.

Four oleanane-type glycosides were isolated from a horticultural cultivar "Green Elf" of the endemic Pittosporum tenuifolium (Pittosporaceae) from New Zealand: three acylated barringtogenol C glycosides from the leaves, with two previously undescribed 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, 3-O-ß-d-galactopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, and the known 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C (Eryngioside L). From the roots, the known 3-O-ß-d-glucopyranosyl-(1→2)-ß-d-galactopyranosyl-(1→2)-ß-d-glucuronopyranosyloleanolic acid (Sandrosaponin X) was identified. Their structures were elucidated by spectroscopic methods including 1D- and 2D-NMR experiments and mass spectrometry (ESI-MS). According to their structural similarities with gymnemic acids, the inhibitory activities on the sweet taste TAS1R2/TAS1R3 receptor of an aqueous ethanolic extract of the leaves and roots, a crude saponin mixture, 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, and Eryngioside L were evaluated.

Millettia dubia De Wild. (Fabaceae): Structural analysis of the oleanane-type glycosides and stimulation of the sweet taste receptors TAS1R2/TAS1R3.

From the root barks of a Central African tree Millettia dubia De Wild. (Fabaceae), ten previously undescribed oleanane-type glycosides were isolated by various chromatographic protocols. Their structures were elucidated by spectroscopic methods, mainly 2D NMR experiments and mass spectrometry, as mono- and bidesmosidic glycosides of mesembryanthemoidigenic acid, hederagenin and oleanolic acid. The stimulation of the sweet taste receptor TAS1R2/TAS1R3 by these glycosides was evaluated, and structure/activity relationships were proposed. Two of them showed an agonist effect on TAS1R2/TAS1R3.

Oleanane-type glycosides isolated from the trunk barks of the Central African tree Millettia laurentii.

Seven previously undescribed oleanane-type glycosides were isolated from the trunk barks of a Central African tree named Millettia laurentii De Wild (Fabaceae). After the extraction from the barks, the isolation and purification of these compounds were achieved using various solid/liquid chromatographic methods. Their structures were established mainly by 1D and 2D NMR (COSY, TOCSY, ROESY, HSQC, HMBC) and mass spectrometry (ESI-MS), as 3-O-ß-D-glucuronopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosylechinocystic acid, 3-O-ß-D-apiofuranosyl-(1 â†’ 3)-ß-D-glucuronopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosylechinocystic acid, 3-O-ß-D-apiofuranosyl-(1 â†’ 3)-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosylechinocystic acid, 3-O-ß-D-apiofuranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 2)]-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosylechinocystic acid, 3-O-ß-D-apiofuranosyl-(1 â†’ 3)-[α-L-arabinofuranosyl-(1 â†’ 2)]-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosylechinocystic acid, 3-O-α-L-arabinofuranosyl-(1 â†’ 2)-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyloleanolic acid, 3-O-ß-D-apiofuranosyl-(1 â†’ 3)-[α-L-arabinofuranosyl-(1 â†’ 2)]-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyloleanolic acid. In addition, the cytotoxicity of six glycosides among the isolated ones, was evaluated against 4 T1 cell line from a mouse mammary gland tissue, using MTS method.

Terpenoid glycosides from the root's barks of Eriocoelum microspermum Radlk. ex Engl.

Eight undescribed triterpenoid saponins together with a known one, and two undescribed sesquiterpene glycosides were isolated from root's barks of Eriocoelum microspermum. Their structures were elucidated by spectroscopic methods including 1D and 2D experiments in combinaison with mass spectrometry as 3-O-α-L-rhamnopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 3)-[ß-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 3)-[ß-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin 28-O-ß-D-glucopyranosyl ester, 3-O-α-L-rhamnopyranosyl-(1 → 3)-ß-D-xylopyranosyl-(1 → 4)-ß-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 3)-α-L-arabinopyranosyl-(1 → 4)-ß-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosylhederagenin, 3-O-ß-D-xylopyranosyl-(1 → 4)-α-L-arabinopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 3)-α-L-arabinopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin, 1-O-{ß-D-xylopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-ß-D-glucopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 6)}-[ß-D-xylopyranosyl-(1 → 3)]-[α-L-rhamnopyranosyl-(1 → 2)]-ß-D-glucopyranosyl-(2E,6E)-farnes-1-ol, 1-O-{ß-D-glucopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-ß-D-glucopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 6)}-[ß-D-xylopyranosyl-(1 → 3)]-[α-L-rhamnopyranosyl-(1 → 2)]-ß-D-glucopyranosyl-(2E,6E)-farnes-1-ol. These results represent a contribution to the chemotaxonomy of the genus Eriocoelum highlighting farnesol glycosides as chemotaxonomic markers of the subfamily of Sapindoideae in the family of Sapindaceae.

Triterpenoid saponins from the roots of Spergularia marginata.

Phytochemical investigations of the roots of Spergularia marginata had led to the isolation of four previously undescribed triterpenoid saponins, a known one and one spinasterol glycoside. Their structures were established by extensive NMR and mass spectroscopic techniques as 3-O-ß-D-glucuronopyranosyl echinocystic acid 28-O-α-L-arabinopyranosyl-(1 â†’ 2)-α-L-rhamnopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L- arabinopyranosyl ester, 3-O-ß-D-glucopyranosyl-(1 â†’ 3)-ß-D-glucuronopyranosyl echinocystic acid 28-O-α-L-arabinopyranosyl-(1 â†’ 2)-α-L-rhamnopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)- α-L-arabinopyranosyl ester, 3-O-ß-D-glucopyranosyl-(1 â†’ 4)-3-O-sulfate-ß-D-glucuronopyranosyl echinocystic acid 28-O-α-L-arabinopyranosyl-(1 â†’ 2)-α-L-rhamnopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosyl ester, and 3-O-ß-D-glucopyranosyl-(1 â†’ 4)-ß-D-glucuronopyranosyl 21-O-acetyl acacic acid. Their cytotoxicity was evaluated against two human cancer cell lines SW480 and MCF-7. The most active compound showed a cytotoxicity with IC50 14.2 ± 0.8 µM (SW480), and 18.7 ± 0.8 µM (MCF-7), respectively.

New pregnane and phenolic glycosides from Solenostemma argel.

From the aerial parts, pericarps and roots of Solenostemma argel, three new pregnane glycosides (1-3) with two known ones and a new phenolic glycoside (4) have been isolated. Their structures were established by extensive 1D - and 2D NMR and mass spectroscopic analysis. The cytotoxicity of all compounds was evaluated against two human tumor cell lines (SW 480, MCF-7), but none of them was active in the concentration range 0.9-59.0µM. Compounds 2 and the known argeloside F at non toxic concentrations for the PBMCs (27.3µM and 27.6µM, respectively) significantly decreased the Il-1ß production by LPS-stimulated PBMCs. All isolated compounds showed a significant antioxidant potential with ORAC values in the concentration range 3481-9617µmoleq. Trolox/100g.

A New Aromatic Compound from the Stem Bark of Terminalia catappa.

A new aromatic compound 3,4,5-trimethoxyphenyl-1-O-(4-sulfo)-ß-D-glucopyranoside (1), in addition to two triterpenoid saponins (chebuloside II, arjunoglucoside II), two triterpenes (arjunolic acid and 3-betulinic acid) and sitosterol-3-O-ß-D-glucopyranoside have been isolated from the barks of Terminalia catappa. Their structures have been established on the basis of spectroscopic techniques (1D/2D NMR) and MS. Their cytotoxicity and antiinflammatory activity, together with the antioxidant capacity of compound 1 were also evaluated.

Triterpenoid saponins from the roots of two Gypsophila species.

Two triterpenoid saponins with two known ones have been isolated from the roots of Gypsophila arrostii var. nebulosa, and two new ones from the roots of Gypsophila bicolor. Their structures were established by extensive NMR and mass spectroscopic techniques as 3-O-ß-d-galactopyranosyl-(1→2)-[ß-d-xylopyranosyl-(1→3)]-ß-d-glucuronopyranosylquillaic acid 28-O-ß-d-xylopyranosyl-(1→4)-[ß-d-glucopyranosyl-(1→3)]-α-l-rhamnopyranosyl-(1→2)-[ß-d-glucopyranosyl-(1→4)]-ß-d-fucopyranosyl ester (1), 3-O-ß-d-galactopyranosyl-(1→2)-[ß-d-xylopyranosyl-(1→3)]-ß-d-glucuronopyranosylgypsogenin 28-O-ß-d-xylopyranosyl-(1→4)-[ß-d-glucopyranosyl-(1→3)]-α-l-rhamnopyranosyl-(1→2)-[ß-d-glucopyranosyl-(1→4)]-ß-d-fucopyranosyl ester (2), 3-O-ß-d-galactopyranosyl-(1→2)-[ß-d-xylopyranosyl-(1→3)]-ß-d-glucuronopyranosylgypsogenin 28-O-ß-d-xylopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-[(4-O-acetyl)-ß-d-quinovopyranosyl-(1→4)]-ß-d-fucopyranosyl ester (3), gypsogenic acid 28-O-ß-d-glucopyranosyl-(1→3)-{6-O-[3-hydroxy-3-methylglutaryl]-ß-d-glucopyranosyl-(1→6)}-ß-d-galactopyranosyl ester (4). Three compounds were evaluated against one human colon cancer cell line SW480 and one rat cardiomyoblast cell line H9c2.

cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-ones: synthesis and cytotoxicity in human cancer cell lines in vitro.

A novel family of cisplatin-type complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-one topoisomerase inhibitor via a polymethylene chain and their nonplatinated counterparts were prepared. Their potential cytotoxicity was assessed in three human colorectal cancer cell lines HCT 116, SW480 and HT-29 and compared to the reference molecules cisplatin and oxaliplatin. Platinated compounds were poorly active whilst nonplatinated dibenzo[c,h][1,6]naphthyridin-6-one moieties exhibited higher cytotoxic properties than cisplatin and oxaliplatin whatever the length of the polymethylene chain; molecules containing the tri- and hexamethylene chain length were the most cytotoxic.

Steroidal saponins from Dracaena marginata.

Three new steroidal saponins and ten known ones were isolated from the bark of Dracaena marginata, along with two known steroidal saponins from the roots. Their structures were elucidated on the basis of extensive 1D and 2D NMR experiments and mass spectrometry as (25R)-26-(beta-D-glucopyranosyloxy)3beta,22alpha-dihydroxyfurost-5-en-1beta-yl O-alpha-L-rhamnopyranosyl-(1 --> 2)-[alpha-L-rhamnopyranosyl-(1 --> 4)]-beta-D-glucopyranoside (1), (25R)-26-(beta-D-glucopyranosyloxy)-3beta,22alpha-dihydroxyfurost-5-en-1beta-yl O-alpha-L-rhamnopyranosyl-(1 --> 2)-4-O-sulfo-alpha-L-arabinopyranoside (2), and (25S)-3beta-hydroxyspirost-5-en-1beta-yl O-alpha-L-rhamnopyranosyl-(1 --> 2)-4-O-sulfo-alpha-L-arabinopyranoside (3).

Synthesis, cytotoxicity and structure-activity relationships between ester and amide functionalities in novel acridine-based platinum(II) complexes.

In order to improve the pharmacological profile of the anticancer drug cisplatin, several new acridine-based tethered (ethane-1,2-diamine)platinum(II) complexes connected by a polymethylene chain were synthetized. Activity-structure relationship between amide or ester functionalities was explored by changing acridine-9-carboxamide into acridine-9-carboxylate chromophore. The in vitro cytotoxicity of these new complexes was assessed in human colic HCT 116, SW480 and HT-29 cancer cell lines. Series of complexes bearing the acridine-9-carboxylate chromophore displayed higher cytotoxic effect than acridine-9-carboxamide complexes, with gradual effect according to the size of the polymethylene linker.

Solanum incanum and S. heteracanthum as sources of biologically active steroid glycosides: confirmation of their synonymy.

A new spirostanol saponin (1), along with four known saponins, dioscin (2), protodioscin (3), methyl-protodioscin (4), and indioside D (5), and one known steroid glycoalkaloid solamargine (6) were isolated from the two synonymous species, Solanum incanum and S. heteracanthum. The structure of the new saponin was established as (23S,25R)-spirost-5-en-3ß,23-diol 3-O-{ß-D-xylopyranosyl-(1→2)-O-α-L-rhamnopyranosyl-(1→4)-[O-α-L-rhamnopyranosyl-(1→2)]-ß-D-glucopyranoside}, by using a combination of 1D and 2D NMR techniques including (1)H, (13)C, COSY, TOCSY, NOESY, HSQC and HMBC experiments and by mass spectrometry. The compounds 1, 3, 4 and 5 were evaluated for cytotoxicity against five cancer cell lines and for antioxidant and cytoprotective activity.

Triterpene saponins from Cyclamen persicum.

A new triterpene saponin 3-O-beta-D-glucopyranosyl-(1 --> 4)-alpha-L-arabinopyranosyl-16alpha-hydroxy-13beta,28-epoxy-oleanan-30-al (1), along with four known triterpene glycosides (2-5) were isolated from Cyclamen persicum. Their structures were characterized by a combination of 1D- and 2D-NMR (1H-1H COSY, TOCSY, NOESY, HSQC, and HMBC) and MS spectrocopic data. The cytotoxicity of compounds 2 and 4 was evaluated using two human colon cancer cell lines HT-29 and HCT 116.

The targeting of surface modified silica nanoparticles to inflamed tissue in experimental colitis.

One aspect in the emerging field of nanomedicine is site specific drug delivery via nanoparticles. The use of nanoparticles allows for increased therapeutic efficiency with a lowered risk for and extent of adverse reactions resulting from systemic drug absorption. 5-Amino salicylic acid (5ASA) loaded silica nanoparticles (SiNP) are proposed here as drug delivery system for specific accumulation in inflamed colonic tissues allowing for selective medication delivery to such inflammation sites. The drug was covalently bound to SiNP by a four-step reaction process. In-vitro toxicity of modified SiNP was tested in appropriate cell culture systems, while targeting index and therapeutic efficiency were evaluated in a pre-existing colitis in mice. Particle diameter was around 140 nm after final surface modification. In-vitro drug release demonstrated significant drug retention inside the NP formulation. Toxicity of the different formulations was evaluated in-vitro cell culture exhibiting a lowered toxicity for 5ASA when bound to SiNP. In-vivo, oral SiNP were found to accumulate selectively in the inflamed tissues allowing for significant amounts of drug load. SiNP demonstrated their therapeutic potential by significantly lowering the therapeutically necessary drug dose when evaluating clinical activity score and myeloperoxidase activity (untreated control: 28.0+/-5.0 U/mg; 5ASA-solution (100mg/kg): 8.2+/-3.4 U/mg 5ASA-SiNP (25mg/kg): 5.2+/-2.4 U/mg). SiNP allow to combine advantages from selective drug targeting and prodrugs appearing to be a promising therapeutic approach for clinical testing in the therapy of inflammatory bowel disease.

5-amino salicylic acid bound nanoparticles for the therapy of inflammatory bowel disease.

Nanoparticles (NP) are known for their specific accumulation in the inflamed tissues in the colon and may therefore allow a selective delivery to the site of inflammation including a reduction of adverse effects. 5-amino salicylic acid (5ASA) loaded NP were designed in order to investigate their therapeutic potential in the treatment of inflammatory bowel disease. 5ASA was covalently bound to poly(caprolactone) prior to all formulation steps. Oil/water emulsification or nanoprecipitation methods were used for the NP formulation. Particle diameters were either 200 or 350 nm for emulsification or nanoprecipitation, respectively. In-vitro drug release demonstrated a significant drug retention inside the NP formulation. Toxicity of the different formulations was evaluated on Caco-2 and HEK cell culture which was slightly increased for 5ASA grafted NP in comparison to blank NP (Me5ASA-NP: 75 microg/l; blank NP: 210 microg/l). In-vivo, clinical activity score and myeloperoxidase activity decreased after administration of all 5ASA containing formulations (untreated control: 28.0+/-5.6 U/mg; 5ASA-NP (0.5 mg/kg): 15.2+/-5.6 U/mg; 5ASA solution (30 mg/kg): 16.2+/-3.6 U/mg). NP formulations allowed to lower significantly the dose of 5ASA. These oral NP formulations demonstrated their therapeutic potential and appear to be an interesting approach for the therapy of inflammatory bowel disease.